Dendritic macromolecules, sometimes referred to as dendrimers, are three-dimensional, highly ordered oligomeric and polymeric molecules with a very good defined chemical structure. Some dendritic macromolecules are known and are described, for example, in Angew. Chem. Int. Ed. Engl., 29: 138-175 (1990), the disclosure of which is incorporated herein by reference. This article describes a number of different dendritic macromolecules, for example polyamidoamine (PAMAM) dendrimers, which are also described in U.S. Pat. No. 4,507,466, and polyethyleneimine (PEI) dendrimers, which are also described in U.S. Pat. No. 4,631,337.
The applications envisaged for dendritic macromolecules are as diverse as they are numerous. The aforementioned publications mention several possible applications such as, for example, electronic applications, applications for the calibration of sieves, catalysts (and catalyst supports), selective membranes and coatings, but applications as impact modifiers or as cross-linking agents in several plastics could also be considered.
A drawback of the aforementioned dendritic macromolecules, however, is that PAMAM dendrimers are very sensitive to degradation through hydrolysis reactions. In particular, these dendrimers are not stable at an elevated temperature, which means that these macromolecules degrade significantly when they are exposed to higher temperatures.
The heretofore known procedures for preparing dendritic macromolecules also suffer from drawbacks. For instance, the two procedures described in Angew. Chem. Int. Ed. Engl. 29:138-175 (1990) are incapable of being scaled-up to provide commercially useful quantities of dendritic macromolecules. During one synthesis procedure, the so-called `protected group method`, the composition of the dendritic macromolecules, i.e., polyethyleneimine (PEI) dendrimers, is very accurately controlled via the strategic use of protected groups, which prevents undesired side reactions and undesired defects in the structure of the dendritic macromolecules. During the other synthesis procedure, the so-called `excess reagent method`, with which for example polyamidoamine (PAMAM) dendrimers are prepared, a very large excess of reagents is used to statistically minimize the risk of undesired reactions and defects.
The aforementioned `protected group method` is based on the presence of protected aziridine rings. The aziridine rings are opened with the aid of primary amines, after which the deprotection is effected with the aid of a strong acid. The complex isolation procedures, the low yield of the synthesis procedure and the use of expensive reagents renders this method unsuitable for large-scale, e.g., commercially viable preparation of PEI dendrimers.
The aforementioned `excess reagent method` includes, as a reaction step, the complete Michael addition reaction of primary amine groups to methyl methacrylate, followed by amidation using ethylenediamine. However, the synthesis of the polyamidoamine dendrimers thus formed requires a very large excess of reagents to prevent undesired side reactions. The greater part of the excess amount of reagents is removed through evaporation in, for example, a rotary evaporator, after which the last residual amounts of the reagents are removed from the viscous reaction product in a precipitation step. The intermediate product between the various synthesis steps must, however, be completely pure, which means that the precipitation step has to be repeated several times. These complicating factors render this synthesis procedure for dendritic macromolecules also unsuitable for large-scale application.
The drawbacks of each of the aforementioned synthesis procedures are so great that the use of these procedures on a large--and hence commercially attractive scale--involves insurmountable problems. "The main stumbling block to most of these applications is that large-scale synthetic methods remain to be developed." Science 251:1562-1564 (March 1991).